Cigarette smoking is the leading cause of preventable death in the United States, accounting for nearly 443,000 deaths annually. Unfortunately, smoking cessation rates remain low and relapse is common. There is growing consensus that significant strides in helping smokers quit will likely be found in the ability to develop novel, specialized treatments that target the particular needs of subgroups of smokers, especially those who are at higher risk for relapse. One promising line of research in this domain has begun to study panic-prone and anxiety disordered populations, given (a) rates of smoking are double to that of non-psychiatric populations and (b) evidence that panic attacks and anxiety symptoms can significantly impair quit success. Research efforts have aimed to identify explanatory mechanisms that link panic attacks or anxiety states with the re-initiation and maintenance of smoking behavior. Anxiety sensitivity (AS) is a stable, but malleable, is a cognitive-based transdiagnostic construct that has been described as an amplifier of negative states, such anxiety, pain, or stress. Research suggests that smokers with elevated AS may be especially prone to smoke to relieve or avoid distressing bodily and emotional states (e.g., anxiety, panic attacks). Yet, past work on AS and smoking has employed descriptive or correlational methodology; has not directly measured the topography of smoking behavior; and has not integrated the role of acute, panic-relevant states on the relation between AS and smoking motivation (urges, cravings and observable smoking behavior). The current study aims to provide the empirical link between panic-relevant arousal and smoking motivation. It is hypothesized that laboratory-induced panic symptoms will be causally related to an increase in smoking motivation and that AS will moderate this effect. To address these hypotheses, 90 adult smokers (e15 cigarettes per day) will be recruited to participate in a laboratory experiment. Participants will be randomly assigned to inhale a single vital capacity of 35% carbon dioxide [CO2]-enriched air mixture or compressed room air (control condition); this procedure is a safe and frequently used provocation method for panic symptoms. Post-challenge, smoking motivation will be evaluated by self-reported urges and behavioral indices of cravings (latency to smoking) and smoking topography (puff velocity and inter-puff interval - measured by mouthpiece-based, computerized system; Clinical Research Support System). The proposed project will identify factors that increase the risk of drug use and abuse, which addresses the focus of the National Institute of Drug Abuse (NIDA) prevention research goals. Ultimately, in accordance with NIDA's 2010 strategic plan, the proposed study will (1) identify the characteristics and patterns of drug abuse and (2) understand how factors influence the various risk factors for drug abuse. Finally, the award will aid in the ethical, methodological, and substantive training of a promising researcher to address the need for translational, innovative research on tobacco and emotional vulnerability.